Small peptide compositions and uses thereof

Abstract

Interferon-γ-inducible protein 10 (IP-10) peptides, IP-10 peptide variants and in silico designed C-X-C chemokine receptor 3 (CXCR3) peptide agonists are described. The small peptides can be used for inhibiting pathological tissue remodeling and treating fibrosis in a subject, such as a subject with fibrosis of the heart, lung, liver, kidney or skin. The peptide agonists can also be used to treat cardiovascular disease, including myocardial infarction and ischemia-reperfusion injury. Also described are in silico designed peptide antagonists that bind CXCR3 or ligands of CXCR3. These antagonist peptides block CXCR3 signaling by disrupting interaction of CXCR3 with its ligand. Antagonist peptides can be used, for example, to treat myocarditis and atherosclerosis. In additional embodiments agonists and antagonists of CXCR4 are disclosed.

The invention claimed is: 
     
       1. A synthetic peptide 12 to 30 amino acids in length, wherein the synthetic peptide comprises at least 12 consecutive amino acids of any one of SEQ ID NOs: 5-24 and 28-29. 
     
     
       2. The synthetic peptide of  claim 1 , comprising the amino acid sequence of any one of SEQ ID NOs: 5-24 and 28-29. 
     
     
       3. A synthetic peptide 12 to 30 amino acids in length, wherein the synthetic peptide comprises at least 12 consecutive amino acids of any one of SEQ ID NOs: 7, 9, 14, 17, 19 and 35-42. 
     
     
       4. A synthetic peptide comprising the amino acid sequence of any one of SEQ ID NOs: 5-42. 
     
     
       5. The synthetic peptide of  claim 4 , consisting of the amino acid sequence of any one of SEQ ID NOs: 5-42. 
     
     
       6. A composition comprising the synthetic peptide of  claim 4  and a pharmaceutically acceptable carrier. 
     
     
       7. The composition of  claim 6 , wherein the composition further comprises at least one peptide selected from any one of SEQ ID NOs: 1-4. 
     
     
       8. A composition comprising two or more of the synthetic peptides of  claim 4 . 
     
     
       9. An isolated nucleic acid molecule encoding the synthetic peptide of  claim 4 . 
     
     
       10. The isolated nucleic acid molecule of  claim 9 , operably linked to a promoter. 
     
     
       11. A vector comprising the nucleic acid molecule  claim 9 . 
     
     
       12. The vector of  claim 11 , wherein the vector is a viral vector. 
     
     
       13. A composition comprising the synthetic peptide of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
       14. The composition of  claim 13 , wherein the composition further comprises at least one peptide selected from any one of SEQ ID NOs: 1-4. 
     
     
       15. A composition comprising two or more of the synthetic peptides of  claim 1 . 
     
     
       16. A composition comprising the synthetic peptide of  claim 3  and a pharmaceutically acceptable carrier. 
     
     
       17. The composition of  claim 16 , wherein the composition further comprises at least one peptide selected from any one of SEQ ID NOs: 1-4. 
     
     
       18. A composition comprising two or more of the synthetic peptides of  claim 3 .